PROJECT SUMMARY 3,4-Methylenedioxymethamphetamine (MDMA) is a monoamine transporter substrate that stimulates the presynaptic releases of dopamine, serotonin, and norepinephrine. MDMA is a member of the entactogen class of psychoactive substances ? drugs that produce feeling of oneness, emotional openness, and relatedness, as well as empathy and sympathy for others. One unique feature of MDMA and similar drugs from the entactogen class is that people tend to selectively take these drugs in social and/or intimate situations. Indeed, MDMA users typically point to its prosocial and empathy producing effects as a primary reason for its use. Although it is recognized as having significant abuse liability in humans, preclinical studies generally report that it has only weak reinforcing effects and maintains low rates of self- administration in laboratory animals. A significant limitation of these preclinical studies is the need to isolate subjects during test sessions, a necessary requirement of intravenous drug self-administration procedures. We recently developed custom-built, operant-conditioning chambers that permit two rats (or more) to self-administer drugs simultaneously, side-by-side, in the same test chamber. A wire screen permits complete visual, auditory, olfactory, and limited tactile contact between social partners, but prevents one rat from access the response lever and tethering lines of its partner. We have published a series of studies describing the use of these chambers in rats self-administering cocaine, and have demonstrated that intake increases when a social partner also has access to cocaine but decreases when a partner does not have access to cocaine. We have also shown that rats prefer to respond on a lever in close physical proximity to another rat self-administering cocaine, and that rats develop a preference for another rat with a similar history of cocaine self-administration in partner preference tests. The objective of this project is to examine the acquisition and maintenance of MDMA self-administration in a translationally relevant model of the social environment, and to determine whether MDMA influences choice of social partners. To this end, Aim 1 will examine the acquisition and maintenance of MDMA self- administration in three groups of experimentally nave rats: (1) rats tested in isolation, (2) rats tested in the presence of another rat that has access to MDMA and has previously been trained to self-administer MDMA, and (3) rats tested in the presence of another rat that does not have access to MDMA. Aim 2 will use rats from the first aim to examine whether MDMA influences the choice of a social partner in a partner preference test. In order to increase the translational relevance of our model, experiments will be conducted in male-male, female-female, and male-female social dyads. Collectively, these experiments will identify important social and environmental determinants of MDMA use in human populations.